Differential responses of AMD mitochondrial DNA haplogroups to PU-91, a mitochondria-targeting drug

•This study examined the response(s) of AMD ARPE-19 transmitochondrial cybrids having U, K, and J mtDNA haplogroups to treatment with a mitochondria-targeting PU-91 drug.•PU-91 exerts its cytoprotective effects by upregulating PGC-1α (Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha) which is a primary regulator of the mitochondrial biogenesis pathway.•This study demonstrates that AMD cybrids with different mtDNA haplogroups i.e., U, K, J haplogroups respond differentially to PU-91 drug treatment.•Our study showed that the PU-91 drug increases viable cell number, improves mitochondrial health, and protects AMD cybrids against oxidative stress across the board irrespective of their haplogroup variation.